The compound having a C4 framework represented by Chemical Formula 1, of which both of R1 and R2 are methyl group, can be used very usefully for preparing the medicine (HKI-272, Neratinib) represented by Chemical Formula II shown in Scheme 1 and the medicine (BIBW-2992, Tovok) represented by Chemical Formula III shown in Scheme 2.

wherein, each of R1 and R2 is independently C1-C2 alkyl group, and preferably methyl group all together.


As shown in Scheme 1 and 2, the compound of Chemical Formula 1 is used for preparing the medicines of Chemical Formulae II and III in a form of hydrochloride. The compounds of Chemical Formulae II and III have been used as a HER-2 Tyrosine Kinase Inhibitor, and an anticancer medicine showing a medical activity, and they are known as the compounds having more excellent effect in comparison with side-effect than former other compounds (US 2003/0050222A1, US 2004/0162442 A1, U.S. Pat. No. 7,126,025 B2).
However, the compound of Chemical Formula 1 is scientifically and industrially very interesting and useful compound because there are many limitations for preparing the same. Therefore, a new method for mass-producing the compound of Chemical Formula 1 is needed.
However, there is no technique to mass-produce the compound of Chemical Formula 1 industrially in prior methods except the following Scheme 3 (U.S. Pat. No. 7,126,025, B2).

That is, the compound of Chemical Formula 1 is only prepared by the known method of Scheme 3 so far, but there is a problem of using carbon tetrachloride or benzene those are very toxic to human body as a solvent. In addition to, the method has a disadvantage of that intense reaction is inevitable and it has a danger of explosion in the reaction. Therefore, prior method of preparing the compound of Chemical Formula 1 is very restricted due to the problems, and only the methods those are very difficult to be used for industrial mass-production are known.
Furthermore, prior method of preparing the compound of Chemical Formula 1 has fatal problem of that it is inevitable to generate a large quantity of impurity, and thus the compound of Chemical Formula 1 prepared by the method includes a large quantity of impurity. Therefore, if the physiological active materials of Chemical Formulae II and III were prepared by using the compound of Chemical Formula 1 prepared by the method, each of the reactions varies severely in input of raw and subsidiary materials, etc. in the preparing process. In addition to, huge financial costs are needed for purifying the compound after chemical reaction in order to obtain the target compound having a worth as a medicine to be obtained, because it cannot help preparing the compounds of Chemical Formulae II and III including a large quantity of impurity, as a result.
Furthermore, if the compound of Chemical Formula 1 is prepared according to Scheme 3, it is possible to obtain the target compound, but the compound cannot help including many side products, because it is impossible to predict the equivalent needed in the reaction. Physical re-crystallization method and the like are used as a method of eliminating the side products, but the financial cost for eliminating the same becomes excessive, because the structure of the side product is very similar to the compound of Chemical Formula 1. However, the method of preparing or purifying the compound for reducing the impurity below the level needed by the quality basis of medicine is not found yet.
Namely, it is real state that it is impossible to use the compound for preparing the medicine requiring strict impurity level when the compound is prepared by hydrolyzing the ester with the base compound after the bromination and the amination as shown in Scheme 3. Furthermore, it is another fatal disadvantage of the method that it is impossible to obtain the target compound of Chemical Formula 1 with high purity, because large quantity of 4-dimethylamino-3-hydroxybutyric acid (hereinafter, norcarnitine) hydrochloride having a hydroxyl group at position 3 is prepared as impurity and when hydrolyzing the ethyl ester with the base, and the impurity of bis-compound is prepared by introducing the amine group, as shown in Scheme 3.